Drugs affecting Blood

Blood Clotting

• Blood clots are also called thrombi

• Develop from abnormalities with:

– Blood coagulation

– Blood flow

– Platelet adhesiveness

– Vessel walls

Blood Clotting

• Anticoagulants

– Prevent clot formation by inhibiting clotting factors

• Antiplatelets

– Reduce risk of clot formation by inhibiting platelet aggregation

• Fibrinolytics

– Dissolve clots already formed

Clotting Cascade

Clotting Cascade

• If any factor in the cascade is missing,

blood will not clot (hemophilia)

Venous Thrombi

• Usually form in areas of slow blood flow,

surgical or vein injuries, large venous

sinuses, or pockets formed by valves in

deep veins

• If the clot breaks off, it can travel to the

lung causing pulmonary embolism (PE)

DVT: Deep Vein Thrombosis

• Deep vein thrombosis above the knee is the

most serious and may be fatal

Risk Factors for DVT

• Age over 40

• Bed rest over 4 days

• Estrogen combined

with nicotine

• High dose estrogen

therapy

• Major illness

• Obesity

• Pregnancy

• Previous DVT

• Surgery

• Trauma

• Varicose veins

Laboratory Testing

• Certain lab tests must be done on patients

who are on anticoagulant therapy

Laboratory Testing

• Partial thromboplastin time (PTT) –

affected by heparin

• Prothrombin Time (PT) – affected by

warfarin

• International Normalized Ration (INR)

• Hematocrit

Anticoagulant Agents

• argatroban

• bivalirudin (Angiomax)

• fondaparinux (Arixtra)

• Heparin (protamine sulphate is antagonist)

• lepirudin (Refludan)

• warfarin (Coumadin) (Vit K ,phytonadione is antidot)

Drug

List

Anticoagulant Agents

Low-Molecular-Weight Heparins:

• dalteparin (Fragmin)

• enoxaparin (Lovenox)

• tinzaparin (Innohep)

Drug

List

heparin

• Inhibits thrombin formation preventing clots

from forming

• Only anticoagulant that does not cross the

placenta

• Given for prophylaxis of DVT in

postoperative, bedridden, obese patients,

and others

warfarin (Coumadin)

• Prevents production of vitamin

K-dependent clotting factors

• Prevents future clots with no effect on

existing clots

• Should not be taken with ASA or NSAIDs

Figure 20.14 Heparin- and low-molecular-weight heparin

(LMWH)–mediated inactivation of thrombin or

Factor Xa

Antiplatelet Agents

• aspirin

• clopidogrel (Plavix)

• ticlopidine (Ticlid)

Drug

List

Figure 20.4 Activation and

aggregation of platelets. GP

= glycoprotein.

Figure 20.5 Aspirin irreversibly

inhibits platelet cyclooxygenase-

1.

Figure 20.6 Acetylation of

cyclooxygenase-1 by aspirin.

Figure 20.7 Mechanism of action

of ticlopidine and clopidogrel. GP

= glycoprotein

clopidogrel (Plavix)

• Blocks ADP (adenosine diphosphate)

receptors and prevents platelet adhesion and

aggregation

• Used to prevent MI and stroke

• Major side effect is bleeding

Antiplatelet Agents

Glycoprotein Antagonists:

• abciximab (ReoPro)

• eptifibatide (Integrilin)

• tirofiban (Aggrastat)

Drug

List

Figure 20.8 Mechanism of

action of glycoprotein (GP)

IIb/IIIa–receptor blockers.

Figure 20.10 Formation of fibrin

clot.

Fibrinolytic Agents

• alteplase (Activase)

• reteplase (Retavase)

• streptokinase (Streptase)

• tenecteplase (TNKase)

• urokinase (Abbokinase)

Drug

List

Figure 20.21 Activation of plasminogen by fibrinolytic agents.

Stroke

• The brain is the most oxygen-rich organ

• If cerebral circulation is stopped, the brain

runs out of oxygen within 10 seconds, tissue

dies and does not regenerate

• A stroke is an interruption of oxygen supply

Types of Strokes

• Ischemic Stroke

• Cerebral Hemorrhage

Types of Strokes

• Ischemic Stroke

– Results from obstruction of blood flow due to a

thrombus or emboli lodging in the blood vessel

• Cerebral Hemorrhage

Types of Strokes

• Ischemic Stroke

• Cerebral Hemorrhage

– Involves primary rupture of a blood vessel

– Signs: sudden severe headache, stiff neck,

stupor, or a combination of these

– Effects are long-lasting and irreversible

Stroke Risk Factors

• Modifiable:

– Cigarette smoking

– Coronary artery

disease

– Diabetes

– Excessive alcohol

intake

– Hyperlipidemia

– Hypertension

– Obesity

– Physical inactivity

Stroke Risk Factors

• Non Modifiable

– Age

– Gender

– Genetic predisposition

– Prior stroke

– Race

Stroke Management

• Emphasis is on prevention

– Antiplatelet therapy

Stroke Management

• Emphasis is on prevention

– Antiplatelet therapy

– Anticoagulant therapy

Stroke Management

• Emphasis is on prevention

– Antiplatelet therapy

– Anticoagulant therapy

– Fibrinolytic intervention

Stroke Management

• Emphasis is on prevention

– Antiplatelet therapy

– Anticoagulant therapy

– Fibrinolytic intervention

– Cerebrovascular surgery

Stroke Management

• Emphasis is on prevention

– Antiplatelet therapy

– Anticoagulant therapy

– Fibrinolytic intervention

– Cerebrovascular surgery

– Nonpharmacologic therapy

Stroke Management

• Emphasis is on prevention

– Antiplatelet therapy

– Anticoagulant therapy

– Fibrinolytic intervention

– Cerebrovascular surgery

– Nonpharmacologic therapy

– Poststroke management

Stroke Management

• Emphasis is on prevention

– Antiplatelet therapy

– Anticoagulant therapy

– Fibrinolytic intervention

– Cerebrovascular surgery

– Nonpharmacologic therapy

– Poststroke management

• It is imperative to know the cause of the stroke to

determine treatment

Antiplatelet Agents

• Prevent platelet activation and formation of

platelet plug

– Can interfere with platelet aggregation induced

by ADP (adenosine diphosphate) or

– Interfere with synthesis of thromboxane

Anticoagulant Agents

• Interfere with the synthesis and activation

of the blood’s coagulation factors

• May prevent existing clots from expanding

• Does not reduce existing clots

Fibrinolytic Agents

• Dissolve existing emboli or thrombi

• Indications:

– DVT

– Acute peripheral occlusion

– Acute MI with embolization

– PE

– Coronary embolus

Agents for TIAs and

Stroke Prevention

• aspirin

• aspirin-dipyridamole (Aggrenox)

• clopidogrel (Plavix)

• dipyridamole (Persantine)

• pentoxifylline (Trental)

• ticlopidine (Ticlid)

Drug

List